The chemotherapeutic potential of Boswellia carterii oleoresins
Cancer is a leading cause of death worldwide. Though effective treatments are available and reduce mortality, issues such as debilitating side-effects and drug resistance necessitate a need to develop alternatives. Natural products are a key and diverse source of novel drugs, though many plants remain therapeutically unexplored. Oleoresins from certain species of plants within the genus Boswellia are known to exhibit anti-microbial and anti-inflammatory activity; attributed to a group of compounds known as boswellic acids. Previous studies suggest certain species of Boswellia also exhibit anti-cancer activity and may be a potential chemotherapeutic source. However, research on one species; Boswellia carterii is comparatively limited. Given the chemical profile of Boswellia varies considerably across species, B. carterii may be an underexploited therapeutic source. Therefore, this study aimed to evaluate the anti-cancer potential and chemical profile of B. carterii oleoresin. A methanolic extraction method was optimised to solubilise compounds from B. carterii oleoresin. Subsequently, MTT assay was used to evaluate cytotoxicity, against several cancer cell lines. Equivalent normal cell lines were used to ascertain specificity of action. Flow cytometry was used to measure relative levels of apoptosis and necrosis and for cell cycle analysis. Western blotting was then used to elucidate detailed molecular mechanisms. The chemical composition of the B. carterii oleoresin was analysed using high-performance liquid-chromatography mass spectrometry (HPLC-MS).Methanolic extracts of the B. carterii oleoresin were cytotoxic to all cancer cell types used in the study. This cytotoxicity was time and concentration dependent with IC50 values between 33.34 and 106.34 µg/ml. IC50 values were higher in equivalent normal cell lines, with selectivity indices ranging between 1.75 and 2.68. Propidium iodide and annexin V fluorescence was significantly increased in cancer cells exposed to B. carterii extracts while western blotting revealed significant cleavage of caspases -3, -7, -9, and PARP. Flow-cytometric analysis of cell cycle showed the proportion of cells in sub G1 and G1 phases were significantly increased in all cancer cell types examined. This was associated with downregulation of cyclin D3 and CDK’s 2, 4 and 6. p27 was upregulated. Chemical analysis confirmed the presence of 3-acetyl-11-keto-β-boswellic acid, 3-O-acetyl-α-boswellic acid, 11-keto-β-boswellic acid and α or β-boswellic acid. 82 uncharacterised compounds were also revealed. These data show methanolic extracts of B. carterii oleoresin are specifically cytotoxic to a diverse range of cancer cell types. Cytotoxicity is produced by activation of the intrinsic pathway of apoptosis. Furthermore, altered expression of cell cycle regulatory proteins leads to a G1 cell cycle arrest and cessation of cancer cell division. Boswellic acids likely produce this biological activity, though other, previously unprofiled compounds may contribute.These findings suggest that B. carterii oleoresin is a potential source of novel chemotherapeutics. Furthermore, given the chemical complexity of B. carterii it is likely the entire genus is therapeutically underexploited. Combined, further investigation towards potential novel drug development is justified.
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